We are investigating the interactions of bisulfite with nucleic acids and other important cell components. We wish to understand the nature of the important biochemical effects that bisulfite may induce in living cells, and the exact molecular basis of these effects. A particular emphasis is placed on the genetic properties of bisulfite, which may result from direct reactions with nucleic acids. The following specific investigations will be carried out in the coming year: a) The extent of co-mutagenicity of bisulfite will be explored, using E. coli. Bisulfite will be used in combination with point and frameshift mutagens, as well as activated carcinogens, at various concentrations, and a number of pH values. The mutagenic effects of bisulfite alone under all these combinations will also be examined, to extend the very narrow data base existing in this area. b) Extensive kinetic studies will be carried out on the spontaneous and bisulfite-catalyzed deamination of 5-methyl-deoxycytidine, to estimate the extent to which environmental bisulfite increases the spontaneous reaction. c) Dinucleoside monophosphates, and DNA, modified by transamination with Beta-naphthyl-hydrasine and bisulfite, will be prepared. The conformational properties of these modified substrates will be explored.